NM_001370466.1(NOD2):c.1066G>A (p.Glu356Lys) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 13, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002512788.9

Allele description [Variation Report for NM_001370466.1(NOD2):c.1066G>A (p.Glu356Lys)]

NM_001370466.1(NOD2):c.1066G>A (p.Glu356Lys)

Gene:

NOD2:nucleotide binding oligomerization domain containing 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_001370466.1(NOD2):c.1066G>A (p.Glu356Lys)

HGVS:

NC_000016.10:g.50711058G>A
NG_007508.1:g.18920G>A
NM_001293557.2:c.1066G>A
NM_001370466.1:c.1066G>AMANE SELECT
NM_022162.3:c.1147G>A
NP_001280486.1:p.Glu356Lys
NP_001357395.1:p.Glu356Lys
NP_071445.1:p.Glu383Lys
LRG_177t1:c.1147G>A
LRG_177:g.18920G>A
LRG_177p1:p.Glu383Lys
NC_000016.9:g.50744969G>A
NM_022162.1:c.1147G>A
NM_022162.2:c.1147G>A
NR_163434.1:n.1131G>A
Q9HC29:p.Glu383Lys

Protein change:

E356K; GLU383LYS

Links:

UniProtKB: Q9HC29#VAR_023823; OMIM: 605956.0011; dbSNP: rs104895477

NCBI 1000 Genomes Browser:

rs104895477

Molecular consequence:

NM_001293557.2:c.1066G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370466.1:c.1066G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022162.3:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_163434.1:n.1131G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Blau syndrome (BLAUS)
Synonyms:: Synovitis granulomatous with uveitis and cranial neuropathies; Arthrocutaneouveal granulomatosis; Granulomatosis, familial, Blau type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008523; MedGen: C5201146; Orphanet: 90340; OMIM: 186580

Name:: Regional enteritis
Synonyms:: Enteritis, Granulomatous
Identifiers:: MeSH: D003424; MedGen: C0678202

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000759529	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 13, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 25093298, 25829188, 15812565, 18718560, 19479836, 20565245, 25136265, 27339507, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000759529

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 13, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Blau syndrome polymorphisms in NOD2 identify nucleotide hydrolysis and helical domain 1 as signalling regulators.

Parkhouse R, Boyle JP, Monie TP.

FEBS Lett. 2014 Sep 17;588(18):3382-9. doi: 10.1016/j.febslet.2014.07.029. Epub 2014 Aug 2.

PubMed [citation]

PMID:: 25093298
PMCID:: PMC4158908

Ex vivo and in vitro production of pro-inflammatory cytokines in Blau syndrome.

Galozzi P, Negm O, Greco E, Alkhattabi N, Gava A, Sfriso P, Fairclough L, Todd I, Tighe P, Punzi L.

Reumatismo. 2015 Mar 31;66(4):277-84. doi: 10.4081/reumatismo.2014.772.

PubMed [citation]

PMID:: 25829188

See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000759529.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects NOD2 function (PMID: 25093298, 25829188). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NOD2 protein function. ClinVar contains an entry for this variant (Variation ID: 4701). This missense change has been observed in individual(s) with Blau syndrome (PMID: 15812565, 18718560, 19479836, 20565245, 25136265, 27339507). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 383 of the NOD2 protein (p.Glu383Lys).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2024

ClinVar

Relating variation to medicine